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Biomedical subjects

M Halpern

Publications and source records attributed to M Halpern.

At least 19 recordsLinked to original sources

Predictive value of serum globulin levels for the extent of hepatic fibrosis in patients with chronic hepatitis B infection.

The mechanism underlying disease progression in hepatitis B virus (HBV) infection is unknown. Immunoglobulins stimulate the proliferative activity of rat hepatic stellate cells in vitro. A strong association was found between serum immunoglobulin levels and hepatic fibrosis in patients with hepatitis C virus infection. Our objective was to determine if the same index could also be used in patients with chronic HBV infection. The records of 100 patients with biochemical, serological, virological and histological evidence of chronic HBV infection were reviewed for background factors and serum globulin and immunoglobulin levels. Mean (+/-SD) patient age was 44.0 +/- 14.7 years; 80 (80%) were male. Of the factors found to be significant on univariate analysis, the only significant predictors of severe hepatic fibrosis (stage > or = 2) on multivariate analysis were serum globulin level [odds ratio (OR) 5.97, 95% confidence intervals (CI) 1.82-19.53, P = 0.0004], platelet count (OR 0.98, CI 0.97-0.99, P = 0.001), and immunoglobulin G (IgG) level (OR 1.003, CI 1.000-1.007, P < 0.042) but not IgA, alkaline phosphatase, albumin or international normalized ratio. For each increase of 0.33 mg/dL in serum globulin, there was a 0.5 point increase in the stage of hepatic fibrosis. There appears to be a strong association between levels of serum globulin and IgG and extent of hepatic fibrosis in patients with chronic HBV infection. They can serve as noninvasive markers of hepatic fibrosis and, if confirmed, have important implications for the management of patients with chronic HBV infection.

Adult↗

Neurogenesis, migration, and apoptosis in the vomeronasal epithelium of adult mice.

The location of neurogenesis and the direction of migration of neurons in the adult mouse vomeronasal organ is controversial. Cell division occurs at the center, and particularly, at the edges of the epithelium. Newly generated cells at the center of the epithelium participate in neurogenesis, however, it is unknown to what extent dividing cells at the edges participate in growth, become apoptotic or mature into neurons. Premitotic cells were labeled with bromodeoxyuridine (BrdU) in adult mice and animals allowed to survive for different postinjection periods. The terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end-labeling (TUNEL) method was used to show the distribution of apoptotic cells. The vertical and horizontal position of BrdU-labeled cells was analyzed as a function of postinjection survival time. Vertical and horizontal migration of BrdU-labeled cells were detected. Cells in the central portions of the epithelium migrated vertically to become neurons as demonstrated by co-expression of olfactory marker protein. Cells at the edges migrated horizontally very slowly (less than 10% of the distance from the edge to the center of the epithelium per month), thus indicating that these cells participate in cell renewal exclusively in marginal regions. Neural turnover in the mouse vomeronasal epithelium, therefore appears to occur through a process of vertical migration. Data on the distribution of apoptotic cells indicate that a number of dividing cells throughout the epithelium, but particularly at the edges, die before becoming functional neurons. Accordingly, most dividing cells at the edges probably constitute a reservoir of stem cells dying before differentiation.

Animals↗

Outcome of infections caused by multiple drug-resistant bacteria in liver transplant recipients.

OBJECTIVE: To evaluate the impact of infections caused by multiple-drug-resistant (MDR) bacteria on the clinical outcome of liver transplant recipients. METHODS: Retrospective study including all episodes of bacterial infection diagnosed in patients undergoing liver transplantation from January 19, 1999, to June 30, 2002. The diagnosis of bacterial infection required microbiological documentation. Mortality associated with episodes of infection by MDR bacteria was compared to that observed after antibiotic-susceptible bacterial infections. RESULTS: Among 99 patients undergoing liver transplantation during the study period, there were 57 episodes of bacterial infections. Gram-negative bacilli were the predominant etiologic agents (76%) and Pseudomonas aeruginosa was the most frequent bacterial species found in these cases (23 isolates, 28%). Thirty-six episodes of infection (63%) were caused by MDR bacteria. Mean time after transplantation to the diagnosis of infection was 17 days. Mortality associated with episodes of MDR bacterial infections (nine deaths, 25%) was not significantly different from that observed during episodes of antibiotic-susceptible bacteria (five deaths, 24%; P =.92). CONCLUSION: These data suggest that resistance to multiple antimicrobial agents does not have an impact on the mortality associated to bacterial infections in liver transplant recipients.

Anti-Bacterial Agents↗

Chironomid egg masses as a natural reservoir of Vibrio cholerae non-O1 and non-O139 in freshwater habitats.

Cholera is a diarrheal disease caused by the gram-negative bacterium Vibrio cholerae, and an estimated 120,000 deaths from cholera occur globally every year. The natural reservoir of the bacterium is environmental. A recent report indicated an association between V. cholerae and chironomid egg masses. Chironomids, the "non-biting midges" (Diptera; Chironomidae), are the most widely distributed and frequently the most abundant insects in freshwater. Females attach egg masses, each containing hundreds of eggs encased in a layer of gelatin, to the water's edge where bacteria are abundant and may encounter the nutrient-rich substrate. Here we report the isolation of non-O1 and non-O139 V. cholerae from chironomid egg masses from different freshwater bodies in Israel, India, and Africa. In a yearly survey in Israel, chironomid populations were found to peak biannually, and it seemed that those peaks were followed by subsequent bacterial growth and disappearance during the winter in the Mediterranean region. The bacterial population rose as water temperature surpassed 25 degrees C. Thirty-five different serogroups of V. cholerae were identified among the bacteria isolated from chironomids, demonstrating population heterogeneity. Two strains of V. cholerae O37 and O201 that were isolated from chironomid egg masses in Zanzibar Island were NAG-ST positive. Our findings support the hypothesis that the association found between chironomids and the cholera bacteria is not a rare coincidence, indicating that chironomid egg masses may serve as yet another potential reservoir for V. cholerae.

Africa↗

A pilot study to evaluate the safety and feasibility of the administration of AZT/3TC fixed dose combination to HIV infected pregnant women and their infants in Rio de Janeiro, Brazil.

OBJECTIVES: To evaluate the safety and feasibility of zidovudine and lamivudine (AZT/3TC) given to HIV infected pregnant women and their infants in Rio de Janeiro, Brazil. METHODS: This open label phase II study enrolled 40 HIV infected antiretroviral naive women >or=20 weeks gestation, CD4 <500 cells x10(6)/l, from two public hospitals. TREATMENT: fixed dose AZT 300 mg/3TC 150 mg by mouth every 12 hours until labour; AZT 300 mg by mouth every 3 hours until delivery; infants: AZT 4 mg/kg every 12 hours plus 3TC 2 mg/kg every 12 hours for 6 weeks. Blood haematology and chemistry were monitored; adherence evaluated by pills count; efficacy measured by changes in lymphocyte (CD4) and viral load, and by HIV RNA-PCR tests performed at birth, 6 and 12 weeks, to diagnose infant infection. No women breast fed. RESULTS PATIENT CHARACTERISTICS: mean age 24.48 (SD 3.5) years; gestational age 24.5 (4.5) weeks; AZT/3TC duration 14.4 (4.4) weeks; vaginal delivery: 11/39; caesarean section: 28/39. Entry and pre-labour CD4: 310/486 cells x10(6)/l (p<0.001); entry and pre-labour viral load: 53 818/2616 copies/ml (p<0.001). Thirty nine women tolerated treatment with >80% adherence; one was lost to follow up. Five newborns were excluded from 3TC receipt. All 39 babies were uninfected. Haematological toxicity in newborns was common: anaemia in 27; neutropenia in five (two severe); platelets counts <100000 in two. All values recovered on study completion. CONCLUSIONS: Fixed dose AZT/3TC is well accepted, gives improvements in CD4 and viral load; no infants were HIV infected. Haematological toxicity in infants needs careful monitoring.

Administration, Oral↗

Nuisance chironomids in waste water stabilization ponds: monitoring and action threshold assessment based on public complaints.

Large populations of non-biting midges (Chironomidae) that emerged from waste water stabilization ponds in central Israel created severe nuisance to nearby residents in 1998. A study was begun in summer 1998 to examine the dynamics and phenology of the population as a basis for a successful control strategy. The extensive waste pond area required the development of efficient, reliable and competent sampling methods. The efficiency of four sampling methods was tested: (1) egg-mass counts, (2) larval counts, (3) adult emergence traps, and (4) sampling adults with yellow sticky traps placed on the shoreline. The latter two methods were significantly correlated with and accurately detected midge outbreaks. Yellow sticky traps were safer, easier and more convenient to employ for large scale monitoring. An action threshold was determined based on public complaints that were correlated with the numbers of midges caught by yellow sticky traps.

Animals↗

Immunohistochemical identification of components of the chemoattractant signal transduction pathway in vomeronasal bipolar neurons of garter snakes.

The chemosignal transduction pathway in the vomeronasal sensory epithelium of garter snakes involves activation of G-protein-coupled receptors and subsequent generation of second messengers leading to production of an electrical signal. Calcium imaging experiments demonstrate that ligand binding to the receptor leads to an increase in intracellular calcium and that the phosphatidylinositol-turnover pathway plays a major role in this Ca(2+) increase. Here, we demonstrate, using immunohistochemistry, that IP(3) receptors are largely distributed in dendritic regions of the epithelium, ryanodine receptors are confined to the somata region, and Na(+)/Ca(2+) exchanger protein is expressed throughout the vomeronasal (VN) sensory epithelium.

Animals↗

The protective nature of Chironomus luridus larval tubes against copper sulfate.

The objective of this study was to determine whether the tubes in which Chironomus larvae dwell protect them against chemical toxicants. A laboratory culture of an Israeli benthic midge, Chironomus luridus, was exposed to copper sulfate. Two conditions were tested in bioassay experiments: larvae within silt tubes and larvae without tubes. The non toxic, anionic, fluorescent dye, fluorescein, was used to examine the effect of sub-lethal copper sulfate concentrations on the permeability of cuticular, gill and gut epithelia of the chironomids. Increased cell permeability, which is the cause of cell damage, was reflected by an increase in fluorescence intensity. Following exposure to copper sulfate, higher fluorescence was found in different body compartments: midgut, hindgut, tracheal gills, fat body and muscles, and the Malpighian tubules. The effect was significantly higher in tube-free larvae when compared to silt tube dwelling larvae. We conclude that in addition to its other functions in feeding, respiration, and anti-predation shelter, the Chironomus luridus tube protects its inhabitant from toxins such as copper sulfate.

Analysis of Variance↗

Cell migration to the anterior and posterior divisions of the granule cell layer of the accessory olfactory bulb of adult opossums.

To test the hypothesis that differential addition of new cells occurs in the two functionally distinct divisions of the accessory olfactory bulb (AOB), the addition of bromodeoxyuridine-labeled cells was analyzed in the anterior and posterior subdivisions of the AOB as a function of post-injection survival time (0-11 days). One week postinjection, an increase of cells was detected in the granule layer but not in the glomerular or mitral/tufted cell layers. No evidence for differential addition of cells to the anterior and posterior divisions was observed.

Age Factors↗

Neural substrates for tongue-flicking behavior in snakes.

Snakes deliver odorants to the vomeronasal organ by means of tongue-flicks. The rate and pattern of tongue-flick behavior are altered depending on the chemical context. Accordingly, olfactory and vomeronasal information should reach motor centers that control the tongue musculature, namely, the hypoglossal nucleus (XIIN); however, virtually nothing is known about the circuits involved. In the present work, dextran amines were injected into the tongue of garter snakes (Thamnophis sirtalis) to identify the motoneurons of the XIIN. Tracers were then delivered into the XIIN to identify possible afferents of chemical information. Large injections into the XIIN yielded retrograde labeling in two chemosensory areas: the medial amygdala (MA) and the lateral posterior hypothalamic nucleus (LHN). Smaller injections only yielded labeled neurons in the LHN. In fact, the MA, which receives afferents from the accessory olfactory bulb, the rostroventral lateral cortex, and the nucleus sphericus, projects to the LHN. Injections into the MA did not show terminal labeling in the XIIN but in an area lateral to it. However, injections into the LHN gave rise not only to labeled fibers in the XIIN but also to retrograde labeling in the MA, thus confirming the chemosensory input to LHN. Injecting different fluorescent tracers into the tongue and into the LHN corroborated the projection from the LHN to the XIIN. The present report investigates further connections of the olfactory and vomeronasal systems and describes the afferent connections to XIIN in a nonmammalian vertebrate. The circuit for tongue-flicking behavior described herein should be evaluated using functional studies.

Amygdala↗

Laser soldering of rat skin, using fiberoptic temperature controlled system.

BACKGROUND AND OBJECTIVE: Laser soldering of tissues is based on the application of a biological solder on the approximated edges of a cut. Our goal was to use laser soldering for sealing cuts in skin under temperature feedback control and compare the results with ones obtained using standard sutures. STUDY DESIGN/MATERIALS AND METHODS: Albumin solder was applied onto the approximated edges of cuts created in rat skin. A fiberoptic system was used to deliver the radiation of a CO(2) laser, to heat a spot near the cut edges, and to control the temperature. Laser soldering was carried out, spot by spot, where the temperature at each spot was kept at 65-70 degrees C for 10 sec. RESULTS: The tensile strength of laser-soldered cuts was measured after 3-28 days postoperatively and was found comparable to that of sutured cuts. Histopathological studies showed no thermal damage and less inflammatory reaction than that caused by standard sutures (P = 0.04). CONCLUSIONS: Temperature controlled laser soldering of cuts in rat skin gave strong bonding. The cosmetic and histological results were very good, in comparison to those of standard sutures.

Albumins↗

The test-retest reliability of a new occupational risk factor questionnaire for outcome studies of low back pain.

This study reports the test-retest reliability of a 25-item occupational risk factor questionnaire that can be self-administered in clinical settings and used in outcome studies of low back pain or return to work programs. Subjects were 24 patients (workers on sick leave due to acute low back pain), 29 co-workers on active duty in the same jobs in a utility company, and 53 supervisors. Eighty-six subjects were re-tested within a mean interval of 7-10 days; one group of 20 supervisors was re-tested within 81 days. The questionnaire was self-administered during individual interviews. Reliability was estimated by the kappa statistic as the agreement on the scores within the raters in each group. The agreement ranged from 'slight' (0.15) to 'almost perfect' (0.93) when the re-test interval was less than 43 days. Patients and non-patients were consistent in their assessment of the job demands. rights reserved.

Disability Evaluation↗

Functional assessment taxonomy relevant to low-back impairments.

A taxonomy of functional assessment constructs was developed to help the Social Security Administration refine the measurements of work disability. This report addresses content validity of the new taxonomy by examining the relevance of its constructs to a specific disability, and by examining the relationship between these constructs and constructs in other taxonomies. Seven experts linked the new taxonomy to consequences of low-back impairments. The selected constructs were compared to those reported independently by patients (Harper AC, Harper DA, Lambert L, Andrews HB, Lo SK, Ross FM, Straker LM. Pain 1992; 50(2): 189-195). The International Classification of Impairments, Disabilities and Handicaps served to bridge the two exercises. The findings reveal that it is feasible to use the taxonomy to define the impact of a specific disability and consequently link it to a set of standard measurements. Low-back impairments may be best assessed through measures of physical functional limitations, vocational impact, and interpersonal and emotional behavior. The study did not yield cognitive and intellectual measures that were relevant to this impairment.

Back Injuries↗

Neurogenesis in the vomeronasal epithelium of adult rats: evidence for different mechanisms for growth and neuronal turnover.

The pattern of cell migration during neuronal turnover in the vomeronasal sensory epithelium (VN-SE) is controversial. In mice, proliferating cells were detected at the edges and were described as migrating to the center of the VN-SE. In rats, in addition to proliferating cells at the margins of the epithelium, dividing cells are also present along the entire basal lamina of the VN-SE. In marsupials, dividing cells have also been observed in the margins and in the center of the VN-SE, the latter of which migrate vertically and become neurons. To investigate whether the process of neuronal turnover in placental mammals consists of horizontal and/or vertical migration, and whether or not this process is common to mammals, adult rats were injected with bromodeoxyuridine (BrdU) and allowed to survive for different periods of time. The distribution of BrdU-labeled cells in the horizontal and vertical dimension of the VN-SE was analyzed as a function of time. Both horizontal and vertical migrations of BrdU-labeled cells were detected. Since cells in the center of the VN-SE migrate vertically, and, as demonstrated by coexpression of markers of neuronal maturity and BrdU, become mature one day after undergoing mitosis, it is very likely that these cells participate in neuronal turnover. Conversely, because cells in the margins of the VN-SE stop migrating horizontally on day 14 before they have reached the center of the VN-SE, and since the VN-SE continues to grow during adulthood, it is likely that most of these latter cells constitute pools for growth.

Animals↗

Antimicrobial treatment patterns, resource utilization, and charges associated with acute sinusitis in asthma patients.

Antimicrobial treatment patterns, resource utilization, and charges associated with acute sinusitis in patients with asthma were studied. Asthma patients with at least one claim for acute sinusitis were identified by International Classification of Diseases, 9th Revision code in data for 1992-1994 from a large health care insurer in New England. A sinusitis episode was defined on the basis of the pattern of antimicrobial prescribing. Antimicrobials used to treat sinusitis, rates of resource utilization, and overall charges for therapy were determined. A total of 2,633 sinusitis episodes were identified in the records of 34,348 asthma patients. The most frequently prescribed antimicrobial for initial treatment of acute sinusitis was amoxicillin trihydrate (32.2% of patients). Initial therapy was successful in 2,199 episodes (83.5%), initial therapy failed in 250 episodes (9.5%), and relapse occurred in 184 episodes (7.0%). Successfully treated patients had fewer outpatient visits on average (1.42 per episode) and fewer laboratory and diagnostic tests (0.046) than did patients in whom initial therapy failed (1.76 and 0.056 per episode, respectively) or patients who relapsed (1.68 and 0.049). The mean total charge for sinusitis care was $147.61 per episode for successfully treated patients, $242.95 per episode for patients unresponsive to treatment, and $205.49 per episode for patients who relapsed. Antimicrobial treatment of acute sinusitis varied widely in patients with asthma. Resource utilization was associated with the success of treatment.

Acute Disease↗

Cell turnover in the vomeronasal epithelium: evidence for differential migration and maturation of subclasses of vomeronasal neurons in the adult opossum.

Previous investigations of cell turnover in the mammalian vomeronasal sensory epithelium (VN-SE) raised two issues. First, if, in addition to the already demonstrated vertical migration, horizontal migration from the edges of the VN-SE participates in neuronal replacement. Second, whether or not migration and maturation is differential in upper and lower populations of vomeronasal neurons, since these two cell populations are chemically, physiologically, functionally, and perhaps evolutionarily different. By injecting bromodeoxyuridine (BrdU) into adult opossum (Monodelphis domestica) and permitting different survival times, the pattern of distribution of BrdU-labeled cells was analyzed. No evidence of horizontal migration in neuronal replacement was found. To investigate vertical migration and maturation of subclasses of vomeronasal neurons, double immunohistochemistry of BrdU and markers of the lower (G(oalpha) protein) and upper [G(i2alpha) protein and olfactory marker protein (OMP)] cell populations were performed. Three days after administration of BrdU, some mature neurons were observed in both lower and upper layers of the VN-SE, as demonstrated by coexpression of BrdU with G(oalpha) protein and OMP, respectively. The data on vertical distribution, however, indicate that most of the daughter cells enter the G(oalpha)-protein-expressing zone of the VN-SE by day 5, whereas most daughter cells do not reach the G(i2alpha)-protein-expressing zone until day 7, suggesting that these two populations mature at slightly different rates. These results are the first evidence of differential neurogenesis of subclasses of vomeronasal neurons.

Animals↗

Chemosensitive conductance and inositol 1,4,5-trisphosphate-induced conductance in snake vomeronasal receptor neurons.

Snake vomeronasal receptor neurons in slice preparations were studied using the patch-clamp technique in the conventional and nystatin-perforated whole-cell configurations. The mean resting potential was approximately -70 mV; the average input resistance was 3 GOmega. Neurons required current injection of only 1-10 pA to display a variety of spiking patterns. Intracellular dialysis of 100 microM inositol 1,4,5-trisphosphate (IP(3)) evoked an inward current in 38% of neurons, with an average peak amplitude of 16.4 +/- 2.8 pA at a holding potential of -70mV. Application of 100 microM 3-deoxy-3-fluoro-D-myo-inositol 1,4,5-trisphosphate (F-IP(3)), a derivative of IP(3), also evoked an inward current in 4/8 (50%) neurons (32.6 +/- 58 pA at -70 mV, n = 4). The reversal potentials of the induced components were estimated to be -14 +/- 5 mV for IP(3) and -17 +/- 3 mV for F-IP(3). Bathing the neurons in 10 microM ruthenium red solution greatly reduced the IP(3)-evoked inward current to 1.6 +/- 1.1 pA at -70 mV (n = 6). With Cs(+)-containing internal solution, neither the Ca(2+)-ATPase inhibitor thapsigargin (1-50 microM) nor the Ca(2+)-ionophore ionomycin (10 microM) evoked a significant current response, suggesting that IP(3) can elicit current response in the neurons without mediation by intracellular Ca(2+) stores. Intracellular application of 1 mM cAMP evoked no detectable current response. Extracellular application of chemoattractant for snakes evoked a very large inward current. The reversal potential of the chemoattractant-induced current was similar to that of the IP(3)-induced current. The present results suggest that IP(3) may act as a second messenger in the transduction of chemoattractants in the garter snake vomeronasal organ.

Animals↗